1. Field
The present invention relates to a bio-disc comprising new valve control means and fluid movement system, a bio-disc device including the bio-disc, a bio-driver apparatus, and an assay method using the same. More particularly, the present invention relates to a bio-disc with a lab-on-a-chip for various diagnostic assays, nucleic acid hybridization assays, or immunoassays, a bio-driver apparatus integrated with a controller disc including a controller for the bio-disc, and an assay method using the same.
2. Description of the Related Art
The present invention relates to a continued application of International Patent Application No. PCT/KR02/00126, which was filed 27 Jan. 2002 and claims the priority of Korean Patent Application No. 10-2001-0003956, filed 27 Jan. 2001, and International Patent Application No. PCT/KR02/01035, which was filed 31 May 2002 and claims the priority of Korean Patent Application No. 10-2001-0031284, filed 31 May 2001. International Patent Application No. PCT/KR02/00126 and its priority Korean application are entitled “Nucleic acid hybridization assay method and device using cleavage technique responsive to complementary double strand or single strand of nucleic acids or oligonucleotides”, and International Patent Application No. PCT/KR02/01035 and its priority Korean application are entitled “Micro valve apparatus using microbead and method for controlling the same”. The disclosures of the above previous applications are incorporated herein by reference in their entirety.
The nucleic acid hybridization assay method and device using a cleavage technique responsive to a complementary double strand or single strand of-nucleic acids are applicable to diverse quantitative or qualitative assay devices. In addition, the micro valve is an essential element to control the flow of fluid in a lab-on-a-chip.
The nucleic acid assay device may comprise a detector including an optical device, an electrochemical device, or a capacitance and impedance measurement device to detect or cleaved signal elements. The detected results can be digitized as computer executable software and provided through an established communications network, such as the Internet, to a patient or a doctor. In this manner, a remote diagnostic system ensuring convenience to both patient and doctor can be implemented based on the nucleic acid assay device. A capacitance and impedance measurement for the detector may include interdigitated array electrodes with cleavable signal elements, as disclosed in the previous application.
The present invention relates to a non-optical bio-disc, a bio-disc device, a bio-driver apparatus, and an assay method using the same, which are applicable to various kinds of diagnostic assay devices, nucleic acid hybridization assay devices, and immunoassay devices.
Most clinical diagnostic assay devices developed so far for the detection of small quantities of analytes in fluids are used in serial or parallel connection with multiple-sample preparation and automated reagent addition devices for the simultaneous analysis of numerous test samples with higher efficiency. Such automated reagent preparation devices and automated multiplex analyzers are often integrated into a single device.
Clinical laboratory analyzers of this type can accurately perform hundreds of assays using small quantities of samples and reagents in one hour automatically or semi-automatically. However, these analyzers are expensive and only centralized laboratories and hospitals can afford them. Such centralization necessitates sample transport to the laboratory or hospital and often precludes urgent or emergent analysis of time-critical samples.
Thus, to address these problems, there is an increasing need for clinical analyzers which are cheap and easy-to-handle for everyone, such as clinical analyzers suitable for use at the patient bedside of in the patient's home without dedicated detectors.
<Optical and Non-Optical Bio-Discs>
The standard compact disk is formed from a 12-cm polycarbonate substrate, a reflective metal layer, and a protective lacquer coating. DVD stands for digital video disk, a type of optical disk of the same size as the compact disk, but with significantly greater recording capacity.
The polycarbonate substrate is optical-quality clear polycarbonate. In a standard pressed CD or DVD, the data layer is part of the polycarbonate substrate, and the data are impressed as a series of pits by a stamper during injection molding. In the injection molding process, melted polycarbonate is injected into a mold under high pressure and cooled in a mirror image of the mold or stamper. As a result, reverse pits of the stamper are formed on the polycarbonate disk surface during mastering as binary data. The stamping master is typically glass.
As is widely known to one of ordinary skilled in the art, information written to general optical discs, such as audio CDs, game CDs, refractivity in their dye layer. In a common CD using a differential reflectivity detection method, indentations of pits are formed in the CD to a depth on the order of one-eighth to one-quarter of the wavelength of an incident laser beam. The indentations cause destructive interference in a reflected beam and correspond to bits having a “0” value. Flat areas of the CD reflect the incident laser beam toward a detector and correspond to bits having a “1” value.
U.S. Pat. No. 5,580,696 discloses materials of a dye layer for optical discs using refractivity-based data detection. An optical disk using the dye layer is rotated about a rotary shaft and scanned by laser to read data from the dye layer.
However, a general optical pickup for the above-described optical discs includes both a light emitting unit and a light receiving unit in a single module. In this structure, its optical traveling path is relatively long, and there is a poor sensitivity problem of the light receiving unit. In addition, laser scanning for information reading requires actuating the optical pickup to a predetermined location on an optical disc and rotating the optical disc. Furthermore, when such an optical disc read by laser scanning is applied to a bio-assay device, problems such as physical deformation of probes and inaccurate assay results occur.
Various technologies regarding CD-based assay devices have been disclosed: “Optical confocal compact scanning optical microscope based on compact disc technology” (Applied Optics, Vol. 30, No. 10, 1991), “Gradient-index objectives for CD applications” (Applied Optics, Vol. 26, Issue 7, 1987), and “Miniature scanning optical microscope based on compact disc technology” (Proc. Soc. Photo-opt. instrument Eng. page 1139-1169, 1989).
Patents regarding CD-based assay devices include U.S. Pat. No. 4,279,862 entitled “Centrifugal photometric analyzer” (published on 21 Jul. 1981) and U.S. Pat. No. 4,141,954 entitled “Reaction tube assembly for automatic analyzer” (published on 27 Feb. 1979).
GB 1075800 (published on 12 Jul. 1967), entitled “Disc for centrifuge”, discloses a device for flowing a sample fluid supplied via n inject hole of a disc over its surface by centrifugal force. EP 3335946 (published on 12 Apr. 1965), entitled “Separating disks for centrifuge”, discloses an apparatus for separating fluid samples injected via an inject hole of a disc by inducing flow of the samples through channels or chambers formed in the disc by centrifugal force.
U.S. Pat. No. 4,311,039 (published on 19 Jan. 1982), entitled “Disc centrifuge photosedimentometer”, discloses a disc type chemical assay device using centrifugal force and optical detection.
However, the above-listed conventional assay devices failed to ensure perfect automation in assay and diagnosis and are unsuitable for a lab-on-a-chip.
Unlike the conventional optical discs using differential reflection from physical pits or the refractivity in dye layers, a bio-disc according to the present invention reads information using light transmission, capacitance and impedance measurements, or electrochemical detection, wherein the bio-disc includes chambers as fluid reservoirs and channels as flow paths. Such a bio-disc according to the present invention is referred to as a “non-optical bio-disc”, in contrast to the conventional “optical” bio-discs using the differential reflection of laser light scanned over the bio-disc. The conventional ones could not detect information using light transmission due to their structure which includes a reflective metal layer and a dye layer.
The term “non-optical bio-disc” throughout the specification refers to a bio-disc which allows for selective detection of analytic sites using light transmission, capacitance and impedance measurements, or electrochemical detection, without need to rotate the bio-disc and scan it with laser light. Therefore, the “non-optical bio-disc” of the present invention could involve optical assay detectors.
The term “optical bio-disc” throughout the specification refers to a bio-disc using a common optical pickup scanning laser light over the bio-disc to read data from its differential reflectance.
Common polycarbonate substrates can be modified to suit to bio-discs, which are thin film type assay devices, for detecting a small quantity of an analyte in a fluid sample for the diagnostic purpose. In this case, instead of pits and a dye layer, channels as fluid flow paths and chambers as buffer reservoirs are formed in a surface of a polycarbonate substrate through injection molding. In addition, micro valves for controlling fluid flow through the channel and flow rate and an electronic controlling method of the micro valves are needed.
In a bio-disc according to the present invention, channels as fluid flow paths and chambers as buffer reservoirs may be formed in a silicon wafer using semiconductor manufacturing processes. Such a bio-disc according to the present invention includes an electronic circuit integrated into the silicon wafer to control fluid flow and flow rate.